?This study estimated the number of daily tenofovir disoproxil fumarate/ emtricitabine (TDF/FTC) doses required to achieve and maintain (after discontinuation) intracellular drug concentrations that protect against HIV infection for men who have sex with men (MSM).

From an interplay of UHV-STM imaging and DFT calculations, we have illustrated on-surface formation of polyphenyl chains through a hierarchical reaction pathway involving two different kinds of reactions (Ullmann coupling and cross-dehydrogenative coupling), which will provide a deeper understanding of on-surface chemical reactions and an alternative and efficient strategy to fabricate desired surface molecular nanostructures.

Hyperlipidemia is an important public health problem with increased incidence and prevalence worldwide. Current clinical biomarkers, triglyceride, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol lack the necessary specificity and sensitivity and only increase significantly after serious dyslipidemia. Therefore, sensitive biomarkers are needed for hyperlipidemia. Hyperlipidemia-specific biomarkers would improve clinical diagnosis and therapeutic treatment at early disease stages. The aim of metabolomics is to identify untargeted and global small-molecule metabolite profiles from cells, biofluids, and tissues. This method offers the potential for a holistic approach to improve disease diagnoses and our understanding of underlying pathologic mechanisms. This review summarizes analytical techniques, data collection and analysis for metabolomics, and metabolomics in hyperlipidemia animal models and clinical studies. Mechanisms of hypolipemia and antilipemic drug therapy are also discussed. Metabolomics provides a new opportunity to gain insight into metabolic profiling and pathophysiologic mechanisms of hyperlipidemia.

Abstract Simple and reproducible tools to assess antiretroviral adherence are needed. A level of tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) <1,250?fmol/punch is predicted to identify imperfect adherence. Herein we evaluated TFV-DP in DBS as a measure of adherence among HIV-infected women. DBS and peripheral blood mononuclear cells (PBMCs) were collected twice (?1 week apart) in 35 well-controlled HIV-infected women [median age 42 years, 14 African American/black (AA)] receiving daily coformulated tenofovir/emtricitabine and either atazanavir/ritonavir (n=20) or raltegravir (n=16). TFV-DP in DBS and PBMCs was quantified by LC-MS/MS. Six-month adherence was measured as average days between monthly pharmacy refills. Data were loge transformed for analysis and presented as median (range); the correlation between continuous variables was analyzed using the Pearson correlation coefficient. The average TFV-DP between the two visits (aTFV-DP) in DBS and PBMCs was 1,874 (706-3,776) fmol/punch and 125 (1-278) fmol/10(6) cells, respectively. AA women had lower levels of aTFV-DP in DBS compared to whites (1,660 vs. 1,970?fmol/punch; p=0.04), with a viremic patient having the lowest drug levels (706?fmol/punch). Days between pharmacy refills were 34 (30-54) vs. 30 (26-40) in women with TFV-DP in DBS <1,250 vs. ?1,250?fmol/punch (p=0.006). TFV-DP in DBS was negatively correlated with an increasing number of days between refills (r=-0.56, p=0.002). TFV-DP DBS was a reliable and objective measure of adherence in HIV-infected women based on a strong inverse relationship with pharmacy refill adherence.

A wide area quantum key distribution (QKD) network deployed on communication infrastructures provided by China Mobile Ltd. is demonstrated. Three cities and two metropolitan area QKD networks were linked up to form the Hefei-Chaohu-Wuhu wide area QKD network with over 150 kilometers coverage area, in which Hefei metropolitan area QKD network was a typical full-mesh core network to offer all-to-all interconnections, and Wuhu metropolitan area QKD network was a representative quantum access network with point-to-multipoint configuration. The whole wide area QKD network ran for more than 5000 hours, from 21 December 2011 to 19 July 2012, and part of the network stopped until last December. To adapt to the complex and volatile field environment, the Faraday-Michelson QKD system with several stability measures was adopted when we designed QKD devices. Through standardized design of QKD devices, resolution of symmetry problem of QKD devices, and seamless switching in dynamic QKD network, we realized the effective integration between point-to-point QKD techniques and networking schemes.

Majorana fermions are predicted to localize at the edge of a topological superconductor, a state of matter that can form when a ferromagnetic system is placed in proximity to a conventional superconductor with strong spin-orbit interaction. With the goal of realizing a one-dimensional topological superconductor, we have fabricated ferromagnetic iron (Fe) atomic chains on the surface of superconducting lead (Pb). Using high-resolution spectroscopic imaging techniques, we show that the onset of superconductivity, which gaps the electronic density of states in the bulk of the Fe chains, is accompanied by the appearance of zero-energy end-states. This spatially resolved signature provides strong evidence, corroborated by other observations, for the formation of a topological phase and edge-bound Majorana fermions in our atomic chains.

Study Design. A retrospective study.Objective. To report the clinical outcomes and sagittal kinematics following cervical total disc replacement (TDR). To evaluate the in vivo effect of deviated center of rotation (COR) on flexion/extension range of motion (ROM) at the instrumented level.Summary of Background Data. A few studies showed that the location of COR after cervical TDR deviated from its preoperative location or inherent location in healthy subjects. However, little is known about the effect of deviated COR on ROM at the instrumented level.Methods. A total of 24 patients who underwent C5-C6 single-level TDR with Prestige LP (Medtronic Sofamor Danek, Memphis, TN) were retrospectively included. Japanese Orthopedic Association (JOA) score and visual analogue scale (VAS) were used to assess the clinical outcomes. ROM and COR were measured for radiographic analysis. Patients were categorized into 2 groups according to the change of ROM for further evaluation. Group 1, characterized by decreased postoperative ROM, consisted of 16 patients; group 2, characterized by increased postoperative ROM, consisted of 8 patients.Results. There were 10 males and 14 females. The mean age was 45.05 years, and the mean follow-up time was 15.5 months. The JOA score increased significantly and the neck and arm VAS decreased significantly after cervical TDR. On average, ROM was preserved after cervical TDR. The postoperative COR had a significant cranial shift from its preoperative location. The COR shift in anterior-posterior direction was larger in group 2 than that in group 1. No difference was observed in the COR shift in cranial-caudal direction between the 2 groups.Conclusion. Single-level cervical TDR with Prestige LP obtained satisfactory clinical outcomes and partially restored the natural cervical kinematics. At instrumented level, the deviated COR had a negative correlation with the flexion/extension ROM.

The increasing numbers of cases of wound disease are now posing a big challenge in China. For more convenience of wound patients, wound management in community health care centers under the supervision of a specialist at general hospitals is an ideal solution. To ensure an accurate diagnosis in community health clinics, it is important that "the same language" for wound description, which may be composed of unified format description, including wound image, must be achieved. We developed a wound information management system that was built up by acquisition terminal, wound description, data bank, and related software. In this system, a 3G mobile phone was applied as acquisition terminal, which could be used to access to the data bank. This documentation system was thought to be an appropriate proposal for community wound care because of its objectivity, uniformity, and facilitation. It also provides possibility for epidemiological study in the future.

Most studies addressing the specificity of meridians and acupuncture points have focused mainly on the different neural effects of acupuncture at different points in healthy individuals. This study examined the effects of acupuncture on brain function in a pathological context. Sixteen patients with ischemic stroke were randomly assigned to true point group (true acupuncture at right Waiguan (SJ5)) and sham point group (sham acupuncture). Results of functional magnetic resonance imaging revealed activation in right parietal lobe (Brodmann areas 7 and 19), the right temporal lobe (Brodmann area 39), the right limbic lobe (Brodmann area 23) and bilateral occipital lobes (Brodmann area 18). Furthermore, inhibition of bilateral frontal lobes (Brodmann area 4, 6, and 45), right parietal lobe (Brodmann areas 1 and 5) and left temporal lobe (Brodmann area 21) were observed in the true point group. Activation in the precuneus of right parietal lobe (Brodmann area 7) and inhibition of the left superior frontal gyrus (Brodmann area 10) was observed in the sham group. Compared with sham acupuncture, acupuncture at Waiguan in stroke patients inhibited Brodmann area 5 on the healthy side. Results indicated that the altered specificity of sensation-associated cortex (Brodmann area 5) is possibly associated with a central mechanism of acupuncture at Waiguan for stroke patients.

Objectives. Our study was designed to evaluate the association of single nucleotide polymorphisms (SNPs) of the TLR2 gene with antineutrophil cytoplasmic autoantibodies (ANCAs)-associated vasculitides (AAV) in the northern Han Chinese population. Methods. The TLR2 SNPs rs1898830, rs11938228, rs3804099, rs3804100, and rs7656411 were analyzed in 195 AAV patients [granulomatosis with polyangiitis (GPA), n = 100; microscopic polyangiitis (MPA), n = 76; eosinophilic granulomatosis with polyangiitis (EGPA), n = 19] and 501 ethnically and geographically matched healthy controls. Genetic association analysis was carried out using PLINK (version 1.07). For multiple comparisons, a Bonferroni adjustment was conducted (pc = p*n, where n was the number of tested SNPs). Results. The overall frequencies of alleles and genotypes of TLR2 polymorphisms did not differ significantly between AAV patients and controls. The C allele of rs3804100 and the haplotype (C-C) formed by rs3804100 and rs3804099, however, were over-represented in the MPA patient group (pc = 0.018, pc = 0.016, respectively). Moreover, the frequencies of the C allele of both rs3804100 and rs3804099 were higher in the anti-MPO ANCA positive subgroup vs. healthy controls (pc = 0.003, pc = 0.013, respectively). Conclusions. We conclude that rs3804100 of TLR2 predisposes to MPA in northern Han Chinese. Future studies with larger sample sizes in the northern Han Chinese and other populations are required to extend and verify our current findings.

UV irradiation is known to cause cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs), and plays a large role in the development of cancer. Tumor suppression, through DNA repair and proper cell cycle regulation, is an integral factor in maintaining healthy cells and preventing development of cancer. Transcriptional regulation of the genes involved in the various tumor suppression pathways is essential for them to be expressed when needed and to function properly. BRG1, an ATPase catalytic subunit of the SWI/SNF chromatin remodeling complex, has been identified as a tumor suppressor protein, as it has been shown to play a role in Nucleotide Excision Repair (NER) of CPDs, suppress apoptosis, and restore checkpoint deficiency, in response to UV exposure. Although BRG1 has been shown to regulate transcription of some genes that are instrumental in proper DNA damage repair and cell cycle maintenance in response to UV, its role in transcriptional regulation of the whole genome in response to UV has not yet been elucidated. With whole genome expression profiling in SW13 cells, we show that upon UV induction, BRG1 regulates transcriptional expression of many genes involved in cell stress response. Additionally, our results also highlight BRG1's general role as a master regulator of the genome, as it transcriptionally regulates approximately 4.8% of the human genome, including expression of genes involved in many pathways. RT-PCR and ChIP were used to validate our genome expression analysis. Importantly, our study identifies several novel transcriptional targets of BRG1, such as ATF3. Thus, BRG1 has a larger impact on human genome expression than previously thought, and our studies will provide inroads for future analysis of BRG1's role in gene regulation.

Characterized by chronic inflammation, dysfunction of exocrine glands, and systemic autoimmunity, primary Sjögren syndrome (pSS) is a common autoimmune disease in elderly women. Our study was performed to explore the potential involvement of microRNA (miRNA) in Chinese patients with pSS.

PTEN regulates normal signaling through the B cell receptor (BCR). In systemic lupus erythematosus (SLE), enhanced BCR signaling contributes to increased B cell activity, but the role of PTEN in human SLE has remained unclear. We performed fluorescence-activated cell sorting analysis in B cells from SLE patients and found that all SLE B cell subsets, except for memory B cells, showed decreased expression of PTEN compared with B cells from healthy controls. Moreover, the level of PTEN expression was inversely correlated with disease activity. We then explored the mechanisms governing PTEN regulation in SLE B cells. Notably, in normal but not SLE B cells, interleukin-21 (IL-21) induced PTEN expression and suppressed Akt phosphorylation induced by anti-immunoglobulin M and CD40L stimulation. However, this deficit was not primarily at the signaling or the transcriptional level, because IL-21-induced STAT3 (signal transducer and activator of transcription 3) phosphorylation was intact and IL-21 up-regulated PTEN mRNA in SLE B cells. Therefore, we examined the expression of candidate microRNAs (miRs) that could regulate PTEN: SLE B cells were found to express increased levels of miR-7, miR-21, and miR-22. These miRs down-regulated the expression of PTEN, and IL-21 stimulation increased the expression of miR-7 and miR-22 in both normal and SLE B cells. Indeed, a miR-7 antagomir corrected PTEN-related abnormalities in SLE B cells in a manner dependent on PTEN. Therefore, defective miR-7 regulation of PTEN contributes to B cell hyperresponsiveness in SLE and could be a new target of therapeutic intervention.

The development of near-infrared (NIR) functional fluorescent dyes has gained increasing attention over the last few decades. Herein, we describe the development of a unique type of xanthene-cyanine fused NIR fluorophores, XC dyes, formed by reacting chloro-substituted cyanine with resorcin or its analogues under anhydrous conditions. XC dyes are a hybrid of cyanine and xanthene. The preliminary mechanistic studies indicate that the formation of XC compounds likely includes a sequence of cyclization and oxidation. XC dyes have absorption and emission in the NIR region, and their fluorescence properties can be controlled by modifications of the key hydroxyl and amine groups. The novel XC NIR dyes are advantageous over previously developed merocyanine dyes NIR dyes in their chemical stability against strong nucleophiles. Quantum chemical calculations reveal that the distinct properties of XC and HD dyes can be attributed to their structural differences. By taking advantage of the superior properties of XC dyes, we have further constructed a new NIR fluorescent probe, XC-H2 S, which is capable of monitoring both the concentration- and time-dependent variations of H2 S in living animals, highlighting the value of XC NIR dyes. We expect that the unique XC NIR dyes developed herein will find broader applications than HD NIR dyes as fluorescent platforms for the development of a wide variety of NIR fluorescent probes, in particular, those suitable for targets of interest that have strong nucleophilic character.

Agrocybe aegerita Lectin (AAL) has been identified to have high affinity for sulfated and ?2-3- linked sialic acid glycoconjugates, especially the sulfated and sialyl TF (Thomsen-Friedenreich) disaccharide. This study was conducted to investigate the clinicopathological and prognostic value of AAL in identifying aberrant glycosylation in colorectal cancer (CRC).

We tried to investigate the expression characteristics of KAI1, a suppressor of wide-spectrum tumor metastasis, and vascular endothelial growth factor (VEGF), the most common angiogenesis factor, and then to analyze their diagnostic value for hepatocellular carcinoma (HCC).

The objective of this study was to evaluate the safety and efficacy of allogeneic bone marrow mesenchymal stromal/stem cell transplantation (BM-MSCT) for patients with ursodeoxycholic acid (UDCA)-resistant primary biliary cirrhosis (PBC). Ten patients were enrolled in this trial of BM-MSCT. All patients were permitted to concurrently continue their previous UDCA treatment. The efficacy of BM-MSCT in UDCA-resistant PBC was assessed at various time points throughout the 12-month follow up. No transplantation-related side effects were observed. The life quality of the patients was improved after BM-MSCT as demonstrated by responses to the PBC-40 questionnaire. Serum levels of ALT, AST, ?-GT, and IgM significantly decreased from baseline after BM-MSCT. In addition, the percentage of CD8(+) T cells was reduced, while that of CD4(+)CD25(+)Foxp3(+) T cells was increased in peripheral lymphocytic subsets. Serum levels of IL-10 were also elevated. Notably, the optimal therapeutic outcome was acquired in 3 to 6 months and could be maintained for 12 months after BM-MSCT. In conclusion, allogeneic BM-MSCT in UDCA-resistant PBC is safe and appears to be effective.

The association between breastfeeding status and childhood overweight is inconclusive. The aim of the present study was to investigate the relation between exclusive breastfeeding and childhood overweight risk in children 4-5 y of age in Southeast China. Among 97,424 children enrolled between 1999 and 2009 in the Jiaxing Birth Cohort, 42,550 of them were included in the final analysis with complete records on breastfeeding status and anthropometric measurements at 4-5 y of age (48-60 mo). Overweight and being at risk of overweight were identified as a body mass index (BMI)-for-age Z-score ? 2 and between 1 and 2, respectively. After 4-5 y of follow-up, 4845 (11.4%) children were identified as being at risk of overweight, and 1343 (3.16%) children were overweight. Adjusting for important child and maternal characteristics, longer duration of breastfeeding was associated with lower risk of childhood overweight (P-trend = 0.009) and being at risk of overweight (P-trend < 0.001). Children exclusively breastfed for 3-5 mo and ?6 mo had 13% (RR = 0.87; 95% CI: 0.77, 0.99) and 27% (RR = 0.73; 95% CI: 0.56, 0.95) lower risk of becoming overweight compared with children exclusively breastfed for <1 mo, respectively. In boys, there were inverse associations of 3-5 mo (RR = 0.83; 95% CI: 0.71, 0.98) or ?6 mo (RR = 0.65; 95% CI: 0.47, 0.91) of exclusive breastfeeding against becoming overweight, but there were no significant associations in girls (3-5 mo: RR = 0.96, 95% CI: 0.76, 1.22; ?6 mo: RR = 0.92, 95% CI: 0.60, 1.41). In conclusion, the present findings suggest that longer duration of exclusive breastfeeding is associated with lower risk of becoming overweight in Chinese children.

The treatment of chronic calcaneal osteomyelitis remains a challenge for orthopedic and plastic surgeons. The basis of surgical therapy includes thorough debridement of infected tissue and reconstruction with well-vascularized flaps.

The C3 meta-position of fluorene is utilized to construct high-triplet energy compounds. Incorporating a spiroacridine structure, two new host materials SAFDPA and SAFCz were facilely obtained. Their thermal and photophysical properties are fully investigated. The best efficiencies of 19.4%/21.5% of blue/white devices are achieved by SAFCz.

Osteosarcoma (OS), the most common primary bone malignancy, occurs primarily in adolescents and young adults. In earlier genome-wide association studies, rs7591996, rs10208273, rs17206779 and rs1906953 were identified as candidate loci for OS in Caucasians but the association of these single-nucleotide polymorphisms (SNPs) with OS in a Chinese Han population remains unknown. We measured the frequency of these four variants in a Chinese Han population to better understand the genetic etiology of OS. Polymerase chain reaction sequencing was used to detect the genotypes of four candidate SNPs in peripheral blood samples collected from 168 OS patients and 216 healthy controls. Logistic regression models were used to estimate the odds ratios and 95 % confidence intervals. We found rs1906953 in the glutamate receptor metabotropic 4 (GRM4) gene was associated significantly with OS in our Chinese Han population; as with the other SNPs, however, no statistically significant difference was detected. Further analysis showed the association between rs1906953 and OS was independent of gender and age. The rs1906953 locus was not associated with Enneking stages or tumor location; however, it was associated significantly with OS metastasis and prognosis. The GRM4 gene polymorphism was associated with the susceptibility and metastasis of OS in a Chinese Han population.

Epithelioid angiosarcoma (EAS) is a rare disease which presents a great diagnostic challenge. The present study reports a case of EAS in the kidney in a 75-year-old male who presented with gross hematuria. An abdominal computed tomography scan revealed space-occupying lesions of the right kidney and renal cell carcinoma was suspected. Histological examination of the resected specimens showed pleomorphic epithelioid cells with vesicular nuclei, prominent nucleoli and eosinophilic cytoplasm that lined irregular vascular spaces. Immunohistochemical staining revealed that the tumor cells were positive for AE1/AE3, cytokeratin (CK) 7, vimentin, cluster of differentiation (CD) 31 and E-cadherin, but showed no staining for CD10, CD34, factor VIII, CK20, carcinoembryonic antigen or desmin. Based on the histopathological and immunohistochemical findings, the patient was diagnosed with epithelioid angiosarcoma. Postoperative radiation therapy was administered and no recurrence was observed six months after surgery.

The conventional transcatheter closure of patent ductus arteriosus (PDA) requires femoral artery puncture and angiography for duct anatomic and shunting estimation. If such estimation can be replaced by transthoracic echocardiography (TTE), the procedure will be further simplified, with fewer invasions. This study aimed to examine whether TTE can serve as an alternative to aorta angiography and as a major guidance for transcatheter duct closure. The study enrolled 298 consecutive patients (71 males and 227 females) with PDA. In the study, TTE with combined two-dimensional echocardiography (2DE) imaging and color-coded flow imaging (CDFI) was performed to measure the minimal shunting width (MSW) as the estimated minimal duct size for selection of an Amplatzer duct occluder (ADO) and to monitor the transcatheter duct closure intraprocedurally. The MSW was validated against the duct-stretched diameter (SDD), against the minimal waist diameter of the conical part of a released occluder measured by X-ray spot picture after successful duct closure (SDC), and against the size of the finally used ADO (SADO). Good correlation was found between MSW and SDD [SDD (mm) = 1.31 MSW; r = 0.89; p

Recent rising concern about the cost-effectiveness ratio of total knee arthroplasty (TKA) led us to evaluate this successful procedure from the economic perspective, thereby helping policy-makers to conduct medical resource allocation more effectively and efficiently. However, up to now no study has investigated the influence of patients' psychological factors on their evaluation of TKA's cost-effectiveness. Therefore, we decided to determine whether and how depression, which is a common negative psychological factor in the population undergoing TKA, affects their economic evaluation of the procedure.

IgG4-related disease (IgG4-RD) is a multisystem-involved autoimmune disease. Abnormally activated and differentiated B cells may play important roles. Regulatory B cells (Breg) are newly defined B cell subgroups with immunosuppressive functions. In this study, we investigated the differences of B cell subsets, the expressions of co-stimulatory molecules on B cells, and the function of Breg cells in patients with IgG4-RD, primary Sjögren's syndrome (pSS) as well as in healthy controls (HC).

Hepatocellular carcinoma (HCC) is a globally common neoplasm, with regional metastasis associated with >50% of the tumors. Extrahepatic metastasis is also common, with the lungs, diaphragm, abdominal lymph nodes and bone being the most frequently affected regions. However, to the best of our knowledge, HCC metastasis to the lacrimal gland has not been reported in the literature. Only one case of metastasis to the lacrimal sac from a renal cell carcinoma has been reported. The current study presents the case of a 56-year-old male with ocular symptoms who was eventually diagnosed with HCC. The therapeutic alternatives for such cases are also discussed according to the reviewed literature. Clinicians should be watchful for the appearance of tumors in the lacrimal gland in patients with a history of malignancy.

The objective of this study was to compare combined internal and external fixation (CIEF) with minimally invasive percutaneous plate osteosynthesis (MIPPO) in the treatment of distal third tibial fractures, and explore the benefits and defects of these two techniques.

A catalyst composed of [Pd(?(3)-C3H5)Cl]2 and N,N,N',N'-tetra(diphenylphosphinomethyl)pyridine-2,6-diamine (L) was found to be effective for one-pot synthesis of 2-substituted benzo[b]furans from 2-halophenols and alkynes. For 2-bromo-3-hydroxypyridine, the catalyst loading could be as low as 1 ppm and the turnover number (TON) was up to 870,000.

Myricetina flavonoid compound, has been reported to possess antioxidative, antiproliferative and anti-inflammatory effects. However, no study has yet investigated the effect of myricetin on osteogenic differentiation of human bone marrow stem cells (hBMSCs). This study was designed to investigate the effects of myricetin on osteogenic differentiation of hBMSCs in vitro. Cell viability was analyzed by MTT and osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity assay, Alizarin red S dye, real time-polymerase chain reaction (RT-PCR) and Western blot analysis. We found that the ALP activity and the mineralization of hBMSCs were enhanced by treatment with myricetin. Myricetin increased the mRNA expressions of Osteocalcin (OCN), Collagen type I (COL-I), ALP and Runt-related transcription factor 2 (RUNX2). Additionally, we found that myricetin activated the Wnt/?-catenin pathway and increased the expression of several downstream genes including T-cell factor-1(TCF-1) and lymphoid enhancer factor-1 (LEF-1). Depletion of ?-catenin almost completely blocked the positive role of myricetin on osteogenic differentiation. Taken together, our findings suggest that myricetin enhanced osteogenic differentiation of hBMSCs by activating the Wnt/?-catenin signaling. The study may aid in the development of a therapeutic approach utilizing myricetin for the enhancement of bone health and prevention of osteoporosis.

In ovarian stimulation, a 31-year-old woman with polycystic ovary syndrome was at the risk of developing ovarian hyperstimulation syndrome, follicle aspiration was performed, and eight immature oocytes were collected from follicle fluids. After 28?h in vitro culture, six of them reached MII and were vitrified. The patient failed to conceive in her fresh in vitro fertilization cycle and next two replacement cycles. In the third replacement cycle, a successful pregnancy was obtained by vitrified-thawed oocytes. This case demonstrates that follicular aspiration during follicle selection phase has protective effects against developing ovarian hyperstimulation syndrome, and rescued immature oocytes are viable and could produce promising embryos for live birth.

Alismatis rhizoma or Alisma orientale (Zexie in Chinese), the dried rhizome of Alisma orientale Juzepzuk (Alismataceae), is a well-known traditional Chinese medicine and is used as an agent for diuresis and for excreting dampness in China and Japan. In this paper, we report the diuretic activities of the petroleum ether fraction, the ethyl acetate fraction, the n-buthanol fraction, and the remaining fraction, of the ethanol extract of Alismatis rhizoma (AR).

Autophagy is an intracellular degradation process to clear up aggregated proteins or aged and damaged organelles. The Beclin1-Vps34-Atg14L complex is essential for autophagosome formation. However, how the complex formation is regulated is unclear. Here, we show that Dapper1 (Dpr1) acts as a critical regulator of the Beclin1-Vps34-Atg14L complex to promote autophagy. Dpr1 ablation in the central nervous system results in motor coordination defect and accumulation of p62 and ubiquitinated proteins. Dpr1 increases autophagosome formation as indicated by elevated puncta formation of LC3, Atg14L and DFCP1 (Double FYVE-containing protein 1). Conversely, loss of Dpr1 impairs LC3 lipidation and causes p62/SQSTM1 accumulation. Dpr1 directly interacts with Beclin1 and Atg14L and enhances the Beclin1-Vps34 interaction and Vps34 activity. Together, our findings suggest that Dpr1 enhances the Atg14L-Beclin1-Vps34 complex formation to drive autophagy.

Novel aza-C-disaccharide analogues have been conveniently synthesized by using the isoxazoline-linked C-disaccharide derivatives as the intermediates. Firstly, the CN of isoxazoline was reduced to C-N by using DIBAL-H as reducing agent, then followed by the tandem multi-step reactions through catalytic hydrogenation with Pd(OH)2/C involving debenzylated, reductive cleavage of the N-O, condensation-cyclization of the aldehyde and the in situ generated amine group to form imine CN and then CN hydrogenation to form C-N, thus providing a practical and new access to the synthesis of novel aza-C-disaccharide analogues.

MicroRNA-1 (miR-1) has been shown to function as a critical gene regulator in multiple types of cancers. However, the role of miR-1 in osteosarcoma has not been totally clarified. In the present study, we investigated the effects of miR-1 on osteosarcoma and the underlying mechanism. We found that miR-1 was downregulated in osteosarcoma tissues and osteosarcoma cell lines. Restoration of miR-1 significantly suppressed osteosarcoma cell proliferation by inhibiting cell cycle progression. Mediator complex subunit 1 (Med1) and 31 (Med31) were validated as targets of miR-1 in osteosarcoma by luciferase reporter assay. Downregulation of Med1 and Med31 suppressed the proliferation of osteosarcoma cells, and overexpression of Med1 and Med31 abrogated the effects of miR-1 on cell proliferation. Furthermore, both miR-1 and knockdown of Med1 or Med31 reduced the expression of met proto-oncogene (MET) and blocked the downstream signaling of MET responding to hepatocyte growth factor (HGF). Taken together, the findings of this study suggest that Med1 and Med31 serve as potential gene therapeutic targets in osteosarcoma and miR-1 may prove to be a promising agent.

Novel bi-/tricyclic azasugars fused thiazinan-4-one were conveniently synthesized by the tandem Staudinger/aza-Wittig/cyclization reaction under microwave radiation. The aryl group (phenyl or pyridyl) in mercaptan acid had an important effect on the formation of the diastereomers of the tricyclic hybrids 12b-15b. The new bi/tricyclic azasugars 3a-8a, 4b, 6b, 8b and the known ones 2a, 2b were examined for their HIV reverse transcriptase (RT) inhibitory activities. The result showed that compounds 2a-b, 4a, 4b, 5a, and 6a could effectively inhibit RT activity. Among them, the tricyclic azasugar 5a was the best one with the IC50 value of 0.49 ?M. Structure-activity relationship analysis suggested that the phenyl group in the tricyclic azasugars was benefit for their anti-HIV RT activity.

Novel dimers of triphenylethylene-coumarin hybrid containing one amino side chain were designed and synthesized by the condensation of four dicarboxylic acids with the amino monomeric hybrids catalyzed by HATU and DIPEA at room temperature. The adding order of the reactants had a significant effect on the condensation reaction when the malonic acid was used. The dimeric compounds 7a and 7b linked by the malonic acid, showed a broad-spectrum and good anti-proliferative activity against four tumor cells and low cytotoxicity in osteoblast. UV-vis, fluorescence, and circular dichroism (CD) spectroscopies and thermal denaturation exhibited that compounds 7b, 8b, 9b, and 10b had significant interactions with Ct-DNA by the intercalative mode of binding. Both the DNA binding properties and the anti-proliferative activities would be enhanced by dimerization of the monomeric hybrid with one amino side chain, and were significantly affected by the length of the linker (dicarboxylic acids).

Six 5,9,14,18-tetrathiaheptacene derivatives (1?a-1?f) were synthesized by using a simple ether-ether exchange reaction and fully characterized. In contrast to the planar conformation usually observed in thiophene-fused benzene systems, single-crystal analysis indicates that 7,16-dipropyl-5,9,14,18-tetrathiaheptacene (1?a), 7,16-diphenyl-5,9,14,18-tetrathiaheptacene (1?b), and 7,16-di(4'-chlorophenyl)-5,9,14,18-tetrathiaheptacene (1?c) adopt chair conformations. The as-formed dihedral angle between anthracene and the terminal benzene units are 137.258, 137.855, and 134.912° for 1?a, 1?b, and 1?c, respectively, which is close to the theoretical optimization results (128° for 1?b). Interestingly, the oxidized product of 7,16-di(trifluoromethylphenyl)-5,9,14,18-tetrathiaheptacene (1?e) has a saddle shape, which results in the formation of column-shaped units in the single crystal. The substituents on the side phenyl group have less effect on their UV/Vis absorption spectra, but a distinct redshift that accounts for the intramolecular charge transfer can be observed in the emission spectra. The electrochemical measurements show that all compounds present two oxidation waves. The photoswitching behavior based on 1?a-1?f was further measured and the experimental results suggest that these heteroacene derivatives are promising semiconductor materials for organic electronics.

Increasing evidence has recently demonstrated that soluble heparan sulfate (HS), a degradation product of extracellular matrix produced by elastase, plays a key role in the aggravation of acute pancreatitis (AP) and associated lung injury. However little is known about the detailed mechanism underlying HS-induced inflammatory cascade. Our previous work has provided a valuable clue that a large-conductance K(+) channel (MaxiK) was involved in the HS-stimulated activation of murine macrophages. Here we attempted to ask whether pharmacological inhibition of the MaxiK channel will exert beneficial effects on the treatment of AP and secondary lung injury. The protective effects of paxilline, a specific blocker of MaxiK, on rats against sodium taurocholate induced AP were evaluated. Our data showed that paxilline substantially attenuated AP and resultant lung injury, mainly by limiting the burst of inflammatory responses, as proven by decreased plasma concentrations of tumor necrosis factor-? and macrophage inflammatory protein-2, together with unimpaired pancreatic enzyme activities in rats suffering from AP. Compared with the therapeutic administration, pre-treatment of paxilline showed superior potential to slow down the progress of AP. Furthermore, AP rats received paxilline exhibited improved histopathologic alterations both in the pancreas and the lungs, and even lower lung MPO activity. Taken together, our study provides evidence that MaxiK is involved in the spread of inflammatory responses and the following lung injury during the attack of AP, indicating that this ion channel is a promising candidate as a therapeutic target for AP.

Molecular crowding is a new approach to enhance the retention properties and selectivity of molecularly imprinted polymers. In this work, this concept was first applied to chiral CE to enhance its enantioselectivity. A model system, enantioseparation of salbutamol using hydroxypropyl-beta-cyclodextrin as chiral selector in the presence of dextran or dextrin as crowding-inducing agents, was chosen to demonstrate its potency. Some parameters, especially the concentration of crowding-inducing agents and cyclodextrins were investigated intensively. Moreover, based on fluorescence spectroscopy and affinity CE, it was found that the presence of crowding-inducing agents could promote the association of enantiomers with cyclodextrins and intensify the interacting differences of two enantiomers with cyclodextrins. As a result, the essential concentration of cyclodextrins to make the enantiomers reach baseline separation was significantly decreased with the aid of molecular crowding. This study shows that molecular crowding is an effective strategy to enhance the enantioselectivity of cyclodextrin in chiral CE.

The objective of this study was to prospectively compare intraoperative fluoroscopy time and clinical and radiological results in pediatric femoral shaft fractures treated with titanium elastic nailing (TEN) using a small-incision, blind-hand reduction vs closed reduction. From February 2008 to December 2009, sixty-eight children were enrolled in the study. Patients were divided into 2 groups: group A comprised 34 patients treated with a small-incision, blind-hand reduction technique and group B comprised 34 patients treated with a closed reduction technique. Operative time, intraoperative fluoroscopy time, fracture union time, and complications were recorded in both groups. Clinical and radiological results were assessed using the TEN scoring system. Mean operative time was 30.5±8.5 in group A and 53.0±15.0 minutes in group B, and mean fluoroscopy time was 28.4±18.5 seconds in group A and 65.0±28.5 seconds in group B. Operative time and fluoroscopy time were significantly longer in group B (P

OTUB1 is a member of deubiquitinating enzymes; however, its expression and function in colon cancer are still unclear. The present study aimed at investigating the expression of OTUB1 in colon cancer and the relationship between the expression and some clinicopathologic parameters.

Alismatis rhizoma or Alisma orientale (Zexie in Chinese), the dried rhizome of Alisma orientale Juzepzuk (Alismataceae), is a well-known traditional Chinese medicine and is used as an agent for diuresis and for excreting dampness in Asia and Europe. In this paper, we report the diuretic activities of the ethanol extract (EE) and the aqueous extract (AE) of A. rhizoma (AR).

Positron emission tomography (PET) using (18)F-fluorodeoxyglucose has been widely used for analyzing cellular metabolism. The present study aimed to evaluate the association between the diagnostic value of PET/computed tomography (CT) in patients with post-operative recurrent and metastatic colorectal cancer (CRC), and the different levels of carcinoembryonic antigen (CEA). A total of 105 suspected recurrent and metastatic CRC patients (67 males and 38 females; mean age, 48.5 years) were included in this retrospective study. All the patients underwent PET/CT examination. The differences in the PET/CT diagnostic values of CEA-positive and -negative patients with recurrent CRC following surgery were retrospectively analyzed and compared. Among the 105 CRC patients, 87 exhibited recurrence and metastasis, as confirmed by histopathological diagnosis or clinical follow-up data. By contrast, the PET/CT examination results revealed that 85 cases were true positives (a false positive foci was diagnosed in one of the patients), 18 were true negatives and 2 were false negatives. Correspondingly, the sensitivity and degree of accuracy were 97.7 and 97.1%, respectively. The detection rates of PET/CT for the recurrence and metastases were 85.3% in the CEA-positive group and 75.7% in the CEA-negative group. No significant differences were observed between the two groups. Overall, CEA levels do not help improve the detection rate of PET/CT in the recurrence and metastasis of CRC. PET/CT imaging has a high sensitivity and degree of accuracy in detecting recurrence and metastasis following CRC surgery. Therefore, this method is ideal for monitoring relapsed and metastatic foci of post-operative colon cancer cases.

The polysomnography (PSG) index of the apnea hypopnea index (AHI) is considered the 'gold standard' for stratifying the severity of obstructive sleep apnea (OSA). However, AHI cannot reflect the true characteristic of chronic intermittent hypoxia (CIH), which may trigger systemic inflammation in some OSA patients. High-sensitivity C-reactive protein (hsCRP) is considered a biomarker of systemic inflammation in OSA patients. The aim of the present study was to evaluate the relationship between PSG variables and hsCRP in men with severe OSA. Men with severe OSA (AHI ? 30 events/h) diagnosed by PSG were enrolled. AHI and body mass index were matched between a high hsCRP group (hsCRP ? 3.0 mg/L) and a low hsCRP group. A blood sample was taken for serum hsCRP analysis. Multiple regression analysis was performed to assess independent predictors of high hsCRP. One hundred and fifty-two subjects were enrolled in the study (76 in each group). Mean serum hsCRP was 3.76 ± 2.13 mg/L. The mean percentage of total sleep time spent with SaO2 <90% (TST) in the high hsCRP group was significantly higher than in the low hsCRP group (20.99 ± 18.52 vs. 5.84 ± 7.30, p < 0.001). Multivariate analysis showed that TST was the strongest predictor, contributing to 27.7% of hsCRP variability (? = 0.496, p < 0.01). TST may be superior to AHI for evaluating CIH among OSA patients. The severity of OSA should be stratified by a combination of AHI and other hypoxia variables.

Novel triphenylethylene-coumarin hybrids containing two amino side chains were designed and synthesized. Some of these 3,4-diphenyl coumarins, 7b-c (the double chains at 4-position on 3-,4-phenyl, respectively), and 13b-f (the double chains at 4-position on 3-phenyl and 7-position, respectively), showed a broad-spectrum and good anti-proliferative activity against five tumor cells and low cytotoxicity in osteoblast. UV-vis, fluorescence, and circular dichroism (CD) spectroscopies and thermal denaturation exhibited that compounds 7b (R=piperidinyl), 7e (R=NEt2), and 7f (R=4-methylpiperazinyl) had significant interactions with Ct-DNA by the intercalative mode of binding. Structure activity relationships (SARs) analysis suggested that the location of the two amino alkyl chains would play an important role both in the compounds against tumor cells proliferation and their interactions with DNA.

Cyclin D1 (CCND1) plays a key role in cell cycle regulation. It is a well-established human oncogene which is frequently amplified or overexpressed in cancers. The association between CCND1 G870A polymorphism and cancer risk has been widely assessed. However, a definitive conclusion between CCND1 G870A polymorphism and risk of nasopharyngeal carcinoma (NPC) remains elusive.

We aimed to study the selective pressures interacting on SLC45A2 to investigate the interplay between selection and susceptibility to disease. Thus, we enrolled 500 volunteers from a geographically limited population (Basques from the North of Spain) and by resequencing the whole coding region and intron 5 of the 34 most and the 34 least pigmented individuals according to the reflectance distribution, we observed that the polymorphism Leu374Phe (L374F, rs16891982) was statistically associated with skin color variability within this sample. In particular, allele 374F was significantly more frequent among the individuals with lighter skin. Further genotyping an independent set of 558 individuals of a geographically wider population with known ancestry in the Spanish population also revealed that the frequency of L374F was significantly correlated with the incident UV radiation intensity. Selection tests suggest that allele 374F is being positively selected in South Europeans, thus indicating that depigmentation is an adaptive process. Interestingly, by genotyping 119 melanoma samples, we show that this variant is also associated with an increased susceptibility to melanoma in our populations. The ultimate driving force for this adaptation is unknown, but it is compatible with the vitamin D hypothesis. This shows that molecular evolution analysis can be used as a useful technology to predict phenotypic and biomedical consequences in humans.

Global genome nucleotide excision repair (GG-NER) is responsible for identifying and removing bulky adducts from non-transcribed DNA that result from damaging agents such as UV radiation and cisplatin. Xeroderma pigmentosum complementation group C (XPC) is one of the essential damage recognition proteins of the GG-NER pathway and its dysfunction results in xeroderma pigmentosum (XP), a disorder involving photosensitivity and a predisposition to cancer. To better understand the identification of DNA damage by XPC in the context of chromatin and the role of XPC in the pathogenesis of XP, we characterized the interactome of XPC using a high throughput yeast two-hybrid screening. Our screening showed 49 novel interactors of XPC involved in DNA repair and replication, proteolysis and post-translational modifications, transcription regulation, signal transduction, and metabolism. Importantly, we validated the XPC-OTUD4 interaction by co-IP and provided evidence that OTUD4 knockdown in human cells indeed affects the levels of ubiquitinated XPC, supporting a hypothesis that the OTUD4 deubiquitinase is involved in XPC recycling by cleaving the ubiquitin moiety. This high-throughput characterization of the XPC interactome provides a resource for future exploration and suggests that XPC may have many uncharacterized cellular functions.

Five novel organic conjugated derivatives containing multifraction twisted acene units have been synthesized and characterized. These compounds and the model molecule 2-methyl-5,12-diphenyl-6:7,10:11-bisbenzotetracene emit strong blue light in diluted solution with quantum yields of 0.21-0.67, while in the solid state, except for the 1,2,3,4,5,6-hexa(2-(5,12-diphenyl-6:7,10:11-bis(4-tert-butylbenzo)tetracene))benzene, green luminance is seen. The experimental results also indicate that the multifraction structure leads to a significant fluorescence enhancement (over two times) compared to the monomer, which might be attributed to the formation of delocalized excited state in multibranch structures. The quantum-chemical calculation implies that only two branches are involved in formation of the delocalized system for the multibranched derivatives. Furthermore, the organic light-emitting diode (OLED) devices using compounds 1,4-di(2-(5,12-diphenyl-6:7,10:11-bis(4-tert-butylbenzo)tetracene))benzene, 1,3-di(2-(5,12-diphenyl-6:7,10:11-bis(4-tert-butylbenzo)tetracene))benzene, and 1,3,5-tri(2-(5,12-diphenyl-6:7,10:11-bis(4-tert-butylbenzo)tetracene))benzene as emitters exhibit good electroluminescent performance. Our systematic studies might provide more chances to challenge the rational design and synthesis of new- and high-generation branched dendrimers.

The growth of high-quality single crystals of graphene by chemical vapor deposition on copper (Cu) has not always achieved control over domain size and morphology, and the results vary from lab to lab under presumably similar growth conditions. We discovered that oxygen (O) on the Cu surface substantially decreased the graphene nucleation density by passivating Cu surface active sites. Control of surface O enabled repeatable growth of centimeter-scale single-crystal graphene domains. Oxygen also accelerated graphene domain growth and shifted the growth kinetics from edge-attachment-limited to diffusion-limited. Correspondingly, the compact graphene domain shapes became dendritic. The electrical quality of the graphene films was equivalent to that of mechanically exfoliated graphene, in spite of being grown in the presence of O.

Wheat bran is a traditional Chinese medicine; however, it is mostly used as feedstuff in China. Wheat bran is widely accepted as an important ingredient in many low-glycemic index foods in modern western societies; however, its glycemic control mechanism is unknown.

Cordycepin, a nucleoside derivative isolated from Cordyceps, has been reported to exert anti-inflammatory, antitumor, antidiabetic and renoprotective effects. Osteoarthritis (OA) is a degenerative joint disease with an inflammatory component that drives the degradation of cartilage extracellular matrix. This study aimed to assess the effects of cordycepin on human OA chondrocytes.

Efficient, inexpensive and sensitive assays for the measurement of drugs are of interest for pharmacokinetic and pharmacodynamics (PK-PD) analysis. Dried blood spots (DBS) are a unique bioanaltyical matrix with the potential to fulfill this interest for the measurement of numerous analytes. Here we describe the development and validation of a reversed-phase high performance liquid chromatographic (LC), tandem mass spectrometry (MS/MS) assay for the determination of ribavirin (RBV) in DBS. A 3mm punch from spotted and dried whole blood was extracted in methanol utilizing isotopically labeled internal standard for LC-MS/MS analysis. Validation was performed over a range of 0.05?g/mL to 10.0?g/mL and the method was shown to be precise (coefficient of variation ?15%) and accurate (within ±15% of control). These acceptance criteria were met for hematocrit ranges of 20-54%, for center versus edge punches and for spot volumes from 10 to 60?L. RBV was stable for up to 140 days at room temperature and -20°C as well as for three freeze/thaw cycles. Correlation of RBV in DBS versus in plasma yielded r(2)?0.98 demonstrating that DBS can be used as an alternative to plasma for PK-PD studies in human subjects.

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